We propose to map genes which cause the autosomal dominant neurological diseases episodic ataxia, familial periodic paralysis and paroxysmal dystonic choreoathetosis. These diseases are characterized by episodes of neurologic dysfunction interspersed with symptom-free intervals. For each of these diseases, we have access to families with multiple affected members totalling approximately 250 for all families. Informative families will be typed with cloned DNA probes derived from candidate genes and from arbitrary genomic regions that reveal restriction fragment length polymorphisms (RFLP) with polymorphism information contents (PIC) that generally exceed 0.5. Our proposed studies will contribute to the localization of one or more neurological disease genes and may also indicate to what extent genetic heterogeneity exists within these disease classes. These studies constitute the first step towards the ultimate goal of cloning the genes responsible for the disorders and characterizing the structures and functions of the abnormal gene products and their normal homologs.